Dieneophile

Preference for endo or exo transition state depends on the substitution of the diene, dieneophile and connecting chain. 

Diels-Alder Reactions. Acrolein may participate in Diels-Alder reactions as the dieneophile or as the diene (84—89). 

A process has been disclosed in which the mixture of naphthoquinones is reacted with a diene such as butadiene. Owing to the fact that the undesked product is an unsubstituted naphthoquinone, this dieneophile readily reacts to form a Diels-Alder adduct. By appropriate control of reaction parameters, Htde reaction is observed with the substituted naphthoquinone. Differential solubiUty of the adduct and vitamin allows for a facile separation (57,58). 

For the 2-1-2 pathway the FMO sum becomes (ab — ac) = a b — c) while for the 4 -I- 2 reaction it is (ab-I-ab) — a (2b). As (2b) > (b — c), it is clear that the 4 + 2 reaction has the largest stabilization, and therefore increases least in energy in the initial stages of the reaction (eq. (15.1), remembering that the steric repulsion will cause a net increase in energy). Consequently the 4 - - 2 reaction should have the lowest activation energy, and therefore occur easier than the 2-1-2. This is indeed what is observed, the Diels-Alder reaction occurs readily, but cyclobutane formation is not observed between non-polar dienes and dieneophiles. 

The FMO approach shown in Figure 15.19 again indicates that the 4s - - 2s interaction should lead directly to formation of two new bonding a-bonds, i.e. this is an allowed reaction. The preference for a concerted 4s + 2s reaction is experimentally supported by observations which show that the stereochemistry of the diene and dieneophile is carried over to the product, e.g. a trans,frans-l,4-disubstituted diene... 

Ahern and Gokel (1979) briefly mention that (jE -arenediazocyanides also react with a variety of dienes (cyclopentadiene, cyclohexadiene, butadiene, ( )-piperylene, etc.) in a [4+ 2]-cycloaddition reaction with formation of tetrahydropyridazines (Scheme 6-31). Here the two azo nitrogen atoms of the diazocyanide react as a dieneophile in a bis-aza Diels-Alder reaction. 

The first synthesis of stable 3-hydroperoxy-sultams (24) which are a new class of sultam with oxidising properties, was reported. The synthesis involved oxidation of the isothiazolium salts (23) with hydrogen peroxide in acetic acid. Reduction of (24) with aqueous sodium bisulphite afforded the corresponding novel 3-hydroxysultams whereas thermolysis in ethanol resulted in the elimination of water to give 3-ketone derivatives, which are versatile as dieneophiles <96T783>. 

The aqueous Diels-Alder reaction has also been used for bioconjugate studies. A Diels-Alder reaction of diene oligonucleotides with maleimide dieneophiles was used to prepare oligonucleotide conjugates in aqueous media under mild conditions (Eq. 12.39).102 A Diels-Alder-type cycloaddition of an electronically matched pair of saccharide-linked conjugated dienes and a dienophile-equipped protein was the... 

The Coleman synthesis commenced with a [4+2] cyclization to achieve naphthalene 30 (Scheme 7.4). This convergent process required four steps to obtain diene 27 and five steps to attain dieneophile 28. Three further functional group transformations were required to complete aldehyde 31. This novel process realized the installation of all the carbon and oxygen substituents in a regioselective manner. 

Reaction of furan with a modified vinyl sulfoxide type dieneophile, namely (Z)-3-p-tolylsulfinylacrylonitriles, has been carried out with high reactivity and stereoselectivity . 

More recently, Murakami and co-workers have developed a highly regioselechve method for the synthesis of substituted benzenes, which employs vinylallene derivatives and monosubshtuted alkynes (Eq. 2) [8]. Simple olefins, such as ethylene, are also applicable as dieneophile components, albeit with decreased efficiency (Eq. 3). A mechanistic raho-nale was presented for the proposed catalyhc cycle, which nicely explains the observed regioselectivity (Scheme 12.1). The regiochemical outcome was attributed to steric repulsion between the highly hindered metal center and the alkynyl substituent (20 versus 18). 

PTAD continues to find extensive use, particularly as a dieneophile, but a variety of other reactions have been reported. Treatment of the chalcone (79) with PTAD gives a mixture of the bis(adducts) (81) and (82) presumably via the intermediate (80) (Scheme 13) <91BCJ3188>. Diels-Alder reactions with a variety of dienes have been reported, giving unexceptional products <85JCS(Pl)71>. 

Thiophene 1,1-dioxides, unlike most other thiophene derivatives, are dienes and combine with dieneophiles to form adducts that are prone to retro-cycloaddition, extruding sulfur dioxide in the process (Scheme 6.34b). 

Most cyclopropenes are good dieneophiles. Bicyclo[3.1.0]hex-l,5-ene and bicy-clo[4.1.0]hept-l,6-ene are examples of strained alkenes that cannot be isolated, but can be trapped by diphenylisobenzofuran. A number of bridged bicyclo[ 1.1.0)but-1,3-ene derivatives that cannot be isolated also have been trapped via Diels-Alder... 

Equimolar mixtures of 41 separately and independently with each of the dieneophiles 42, 43, and 44 were examined by differential scanning calorimetry (DSC). The thermograms obtained from these experiments are shown in... 

The smaller the AE, the faster the reaction. Therefore, electron donating groups on the diene and/or electron withdrawing groups on the dieneophile will accelerate the reaction. 

The organotin maleate and maleate half-ester derivatives also exhibit this bleaching effect reportedly by a Diels-Alder addition reaction (18). The reaction is specific to the organotin maleates other organotin carboxylates containing normal dieneophiles fail to produce similar results (19). 

The absolute stereochemistry of chelidonine has been determined by an X-ray crystallographic study of its p-bromobenzoyl ester.382 Further details of the photolysis of the unsaturated amide (151) to the two dimers reported previously (Vol. 10) have been published. Attempts have been made to trap the initial product with dieneophiles with nitrosobenzene, the adduct (152) was obtained, and this was decomposed by heat to form oxochelerythrine.383 A review of methods of synthesis of ( )-corynoline and of 12-hydroxy-, 11 -epi-, and homo-chelidonine has been published.384... 

Acetylenic pyrimidines undergo hetero-Diels-Alder reactions yielding pyrido-fused lactams with recent reports of improved yields using microwave-assisted conditions <2005TL3423>. The use of alkynes as dieneophiles has also been reported in an intramolecular reaction with chloropyrimidine (Scheme 55) <2000SL625>, in this case toward the total synthesis of cerpegin via demethylation. 

The data in Table II demonstrate that the effectiveness for poly (vinyl chloride) stabilization of dibutyltin salts of maleic acid or monoesters of maleic acid is caused by a high rate of reaction with allylic chloride moieties. Thus, it is not necessary to postulate, as has been done several times in the literature, that these compounds are effective because they are dieneophiles and therefore capable of disrupting the long chains of unsaturation responsible for color formation. It is gratifying that the performance of the maleate stabilizers is consistent with the Frye-Horst substitution hypothesis. 

Stabilizers. Ideally, the metallic stabilizer should perform four major functions in a vinyl system (1) HC1 acceptor (2) ultraviolet absorber (3) antioxidant (4) reactive dieneophile. 

TABLE 4.5 Periselectivity in the Reaction of 35 with Varions Dieneophiles... 

Breslow attributed the enhanced rate for the Diels-Alder reaction in water to the hydrophobic effect. In an aqueous environment, nonpolar molecules will aggregate to minimize the unfavorable interaction between the hydrocarbon and water. Engberts argued that there is very little evidence for aggregation of diene/dieneophiles in solution of typical concentration levels. Rather, he invoked... 

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